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(Circulation Research. 2007;101:539.)
© 2007 American Heart Association, Inc.

Editorials

Linking Calsequestrin to Lumenal Control of SR Ca²⁺ Release

Thomas R. Shannon

From the Department of Molecular Biophysics and Physiology, Rush University, Chicago, Ill.

Correspondence to Thomas R. Shannon, Rush University, Department of Molecular Biophysics and Physiology, 1750 W Harrison, Chicago, IL 60612. E-mail tshannon@rush.edu

See related article, pages 617–626

Key Words: adrenergic stimulation • arrhythmia • Ca²⁺ handling • ryanodine receptor • sarcoplasmic reticulum

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The heart, beating constantly over the course of the human lifetime, operates continuously through the process of excitation-contraction coupling. Initiated by a depolarizing influx of Na, a small Ca²⁺ flux across the sarcolemma causes a large release of Ca²⁺ from the sarcoplasmic reticulum (SR). Release of this Ca²⁺ takes place via the ryanodine receptor (RyR), a Ca²⁺ channel within the SR membrane which is gated by cytoplasmic Ca²⁺ ([Ca²⁺]_i).¹ This gating takes place to a small but significant extent even at the relatively low [Ca²⁺]_i found during diastole within the myocyte (SR Ca²⁺ leak).

Among the striking features of this SR Ca²⁺ release is its steep nonlinear dependence on the total concentration of Ca²⁺ found in the lumen of the SR ([Ca²⁺]_SRT). The degree of release at diastolic [Ca²⁺]_i is very low when the [Ca²⁺]_SRT is approximately 50% of the level usually found in an isolated cardiac myocyte.² However, it increases dramatically as [Ca²⁺]_SRT increases toward its normal level.

	Functional Consequences of Luminal Ca2+ Regulation of SR Release

 
Of special interest is the effect of SR [Ca²⁺] on the SR Ca²⁺ leak through the RyR. In the cardiac ventricular myocyte, this leak takes place just under the sarcolemmal membrane, the location of many proteins whose effects are regulated by Ca²⁺. The magnitude of SR Ca²⁺ leak may alter the activity of these proteins. Among the candidate proteins which may be affected by the subsarocolemmal Ca²⁺ is the sodium-calcium exchanger (NCX). This may be particularly relevant in cells from hearts . . . [Full Text of this Article]

Related Article:

Modest Reductions of Cardiac Calsequestrin Increase Sarcoplasmic Reticulum Ca²⁺ Leak Independent of Luminal Ca²⁺ and Trigger Ventricular Arrhythmias in Mice

Nagesh Chopra, Prince J. Kannankeril, Tao Yang, Thinn Hlaing, Izabela Holinstat, Kristen Ettensohn, Karl Pfeifer, Brandy Akin, Larry R. Jones, Clara Franzini-Armstrong, and Björn C. Knollmann
Circ. Res. 2007 101: 617-626. [Abstract] [Full Text] [PDF]

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